Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study
Authors: Maria Lönnrot, Kristian F. Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A. McIndoe, Jorma Toppari, Anette-G. Ziegler, Joseph F. Petrosino, Richard Lloyd, Heikki Hyöty, Marian Rewers, Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Brigitte I. Frohnert, Marisa Stahl, Isabel Flores Garcia, Patricia Gesualdo, Sierra Hays, Michelle Hoffman, Rachel Karban, Edwin Liu, Leila Loaiza, Jill Norris, Holly O’Donnell, Loana Thorndahl, Andrea Steck, Kathleen Waugh, Jorma Toppari, Olli G. Simell, Annika Adamsson, Suvi Ahonen, Mari Åkerlund, Sirpa Anttila, Leena Hakola, Anne Hekkala, Tiia Honkanen, Heikki Hyöty, Jorma Ilonen, Sanna Jokipuu, Taru Karjalainen, Leena Karlsson, Jukka Kero, Jaakko J. Koskenniemi, Miia Kähönen, Mikael Knip, Minna-Liisa Koivikko, Katja Kokkonen, Merja Koskinen, Mirva Koreasalo, Kalle Kurppa, Salla Kuusela, Jarita Kytölä, Jutta Laiho, Tiina Latva-aho, Siiri Leisku, Laura Leppänen, Katri Lindfors, Maria Lönnrot, Elina Mäntymäki, Markus Mattila, Maija Miettinen, Teija Mykkänen, Tiina Niininen, Sari Niisistö, Noora Nurminen, Sami Oikarinen, Hanna-Leena Oinas, Paula Ollikainen, Zhian Othmani, Sirpa Pohjola, Solja Raja-Hanhela, Jenna Rautanen, Anne Riikonen, Minna Romo, Juulia Rönkä, Nelli Rönkä, Satu Simell, Päivi Tossavainen, Mari Vähä-Mäkilä, Eeva Varjonen, Riitta Veijola, Irene Viinikangas, Silja Vilmi, Suvi M. Virtanen, Richard McIndoe, Desmond Schatz, Diane Hopkins, Michael Haller, Risa Bernard, Melissa Gardiner, Ashok Sharma, Laura Jacobsen, Jennifer Hosford, Kennedy Petty, Leah Myers, Chelsea Salmon, Anette G. Ziegler, Ezio Bonifacio, Cigdem Gezginci, Willi Grätz, Anja Heublein, Eva Hohoff, Sandra Hummel, Annette Knopff, Melanie Köger, Sibylle Koletzko, Claudia Ramminger, Roswith Roth, Jennifer Schmidt, Marlon Scholz, Joanna Stock, Katharina Warncke, Lorena Wendel, Christiane Winkler, Åke Lernmark, Daniel Agardh, Carin Andrén Aronsson, Rasmus Bennet, Corrado Cilio, Susanne Dahlberg, Ulla Fält, Malin Goldman Tsubarah, Emelie Ericson-Hallström, Lina Fransson, Emina Halilovic, Gunilla Holmén, Susanne Hyberg, Berglind Jonsdottir, Naghmeh Karimi, Helena Elding Larsson, Marielle Lindström, Markus Lundgren, Marlena Maziarz, Jessica Melin, Caroline Nilsson, Kobra Rahmati, Anita Ramelius, Falastin Salami, Anette Sjöberg, Evelyn Tekum Amboh, Carina Törn, Ulrika Ulvenhag, Terese Wiktorsson, Åsa Wimar, William A. Hagopian, Michael Killian, Claire Cowen Crouch, Jennifer Skidmore, Trevor Bender, Megan Llewellyn, Cody McCall, Arlene Meyer, Jocelyn Meyer, Denise Mulenga, Nole Powell, Jared Radtke, Shreya Roy, Preston Tucker, Dorothy Becker, Margaret Franciscus, MaryEllen Dalmagro-Elias Smith, Ashi Daftary, Mary Beth Klein, Chrystal Yates, Jeffrey P. Krischer, Rajesh Adusumali, Sarah Austin-Gonzalez, Maryouri Avendano, Sandra Baethke, Brant Burkhardt, Martha Butterworth, Nicholas Cadigan, Joanna Clasen, Kevin Counts, Laura Gandolfo, Jennifer Garmeson, Veena Gowda, Christina Karges, Shu Liu, Xian Liu, Kristian Lynch, Jamie Malloy, Lazarus Mramba, Cristina McCarthy, Jose Moreno, Hemang M. Parikh, Cassandra Remedios, Chris Shaffer, Susan Smith, Noah Sulman, Roy Tamura, Dena Tewey, Henri Thuma, Michael Toth, Kendra Vehik, Ponni Vijayakandipan, Melissa Wroble, Jimin Yang, Kenneth Young, Liping Yu, Dongmei Miao, Kathleen Gillespie, Kyla Chandler, Ilana Kelland, Yassin Ben Khoud, Matthew Randell, Stephen S. Rich, Wei-Min Chen, Suna Onengut-Gumuscu, Emily Farber, Rebecca Roche Pickin, Jonathan Davis, Jordan Davis, Dan Gallo, Jessica Bonnie, Paul Campolieto, Joseph Petrosino, Nadim J. Ajami, Richard E. Lloyd, Matthew C. Ross, Jacqueline L. O’Brien, Diane S. Hutchinson, Daniel P. Smith, Matthew C. Wong, Xianjun Tian, Tulin Ayvaz, Auriole Tamegnon, Nguyen Truong, Hannah Moreno, Lauren Riley, Eduardo Moreno, Tonya Bauch, Lenk Kusic, Ginger Metcalf, Donna Muzny, Harsha V. Ardhan Doddapaneni, Richard Gibbs, Chris Deigan, Beena Akolkar, Thomas Briese, Todd Brusko, Teresa Buckner, Suzanne Bennett Johnson, Eoin McKinney, Tomi Pastinen, Steffen Ullitz Thorsen, Erick Triplett
Journal: Diabetes Care (2023)

OBJECTIVE To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort. RESEARCH DESIGN AND METHODS GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study. RESULTS GIE reports (odds ratio [OR] 2.17 [95% CI 1.39–3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36–23.7]) at &amp;lt;1 year of age were associated with an increased IAA risk at 2–4 years of age. GIEs reported at age 1 to &amp;lt;2 years correlated with a lower risk of IAA up to 10 years of age (OR 0.48 [0.35–0.68]). GIE reports at any other age were associated with an increase in IAA risk (OR 2.04 for IAA when GIE was observed 12–23 months prior [1.41–2.96]). Impacts on GADA risk were limited to GIEs &amp;lt;6 months prior to autoantibody development in children &amp;lt;4 years of age (OR 2.16 [1.54–3.02]). CONCLUSIONS Bidirectional associations were observed. GIEs were associated with increased IAA risk when reported before 1 year of age or 12–23 months prior to IAA. Norwalk virus was identified as one possible candidate factor. GIEs reported during the 2nd year of life were associated with a decreased IAA risk.